Systemic lupus erythematosus (SLE) is an autoimmune disease that can severely damage the kidneys, joints, and other tissues. The role of genetic susceptibility in SLE has been extensively examined, but relatively little is known about the contribution of specific hormonal and environmental influences involved in the etiology of SLE. Our study focuses on measures of endogenous hormone exposure (menstrual and reproductive history), exogenous sources of estrogen (including estrogen replacement therapy and fertility drugs), occupational exposures that have been linked to the development of SLE or other autoimmune diseases (e.g., silica dust), and medical history-related factors including infectious diseases, allergies, and transfusions. Manuscripts have been completed and submitted for data analyses and results for medical history-related risk factors, reproductive and hormonal risk factors (including breastfeeding and pre-eclampsia), and smoking and use of hair treatments. Dr. Parks and I are currently working on the analysis of silica exposure from traditional 'dusty trades' and from farm work. Three percent of controls and 8% of cases had ever worked in a "probable" exposure job. Although the prevalence of exposure was lower in women, the positive association was seen both in women and in men. We are currently preparing manuscripts describing the exposure assessment technique used to determine farming-related silica exposure, the association between silica exposure and SLE, and the effect on the observed association of different exposure assessment techniques used to classify silica exposure from industrial and agricultural work. We also examined silica exposure assessment in farming activities by directly measuring respirable silica in the breathing zone of farm workers in eastern North Carolina. Exposure levels varied substantially by task, with the highest levels seen in tasks identified a priori by the expert panel as having a high dust potential. The results of this study were submitted to the American Industrial Hygiene Association Journal, and we were able to use the data to refine our assessment of farming-related silica exposure in the Carolina Lupus Study. All analyses have been conducted stratified by race. Except for transfusions, any exposure associated with SLE in African-Americans was also associated with risk in whites, and the differences in associations between races were not statistically significant. The increased risk experienced by African-Americans also could not be explained by an increased prevalence of the specific risk factors examined. Among controls, the prevalence of the medical, reproductive, and occupational exposures was generally the same or higher in whites compared with African-Americans. Genetic analyses currently completed or underway include genes affecting inflammatory response (e.g., TNF-alpha and TNF-beta, IL-1, nitric oxide production), immune system recognition of antigens (Gm and Km allotypes), hormone sensitivity (androgen receptor repeat length), and metabolism (GSTT1 and GSTM1 null genotypes).